Significance Thrombocytopenia is a common hematologic problem among neonates and of significant clinical importance because of the increased incidence of intracranial hemorrhage and morbidity in thrombocytopenic neonates. Although commonly observed, the pathophysiology is poorly understood. Objectives Very little is known about the role of thrombopoietin (Tpo), a recently discovered physiologic stimulator of platelet production, in thrombocytopenia. Because some groups of thrombocytopenic adults have been shown to respond favorably to the administration of PEG-rHuMGDF, the objective of this study was to determine the safety when administered to newborn rhesus monkeys. Results Eight monkeys were treated subcutaneously with 0, 0.25, 1, or 2.5 5g/kg PEG-rHuMGDF once daily for seven days. Complete blood counts, serum chemistries, clotting panels, and MGDF levels were followed serially, and hematopoietic progenitor cell assays were performed on bone marrow aspirates prior to and post-treatment. All rhesus neonates showed normal growth parameters during the study period, and all chemistries, clotting studies, and blood pressure measurements were normal. The peak serum MGDF concentration was shown to occur at 3 hours, and the half-life was 8.4 to 13 hours. Platelet counts in the treated neonates began to rise on day 6, peaked on day 11, and returned to baseline by day 23. The two highest doses generated an 8- to 12-fold increase in platelets, while those treated with 0.25 5g/kg had a 6-fold increase. All other hematologic parameters measured were unaffected, but induced an increase in the megakaryocyte progenitors in bone marrow. Thus, newborn monkeys responded to doses of PEG-rHuMGDF, and responses were similar to or less than those that were effective in adult animals, without any evidence of adverse effects. Future Directions We will continue to explore safe and efficacious alternatives to platelet transfusions for the management of thrombocytopenia in human neonates. KEY WORDS neonate, monkey, thrombocytopenia, platelets, thrombopoietin FUNDING NIH Grant HL55175, Private Sources